Aim To investigate the effect of DAPT （γ-secretase inhibitor） on the growth of human tongue carcinoma cells and to determine the molecular mechanism to enable the potential application of DAPT to the treatment of t...Aim To investigate the effect of DAPT （γ-secretase inhibitor） on the growth of human tongue carcinoma cells and to determine the molecular mechanism to enable the potential application of DAPT to the treatment of tongue carcinoma. Methodology Human tongue carcinoma Tca8113 cells were cultured with DAPT. Cell growth was determined using Indigotic Reduction method. The cell cycle and apoptosis were analyzed by flow cytometry. Real-time PCR and Immuno-Fluorescence （IF） were employed to determine the intracellular expression levels. Results DAPT inhibited the growth of human tongue carcinoma Tca8113 cells by inducing G0-G1 cell cycle arrest and apoptosis, The mRNA levels of Hairy/Enhancer of Split-1 （Hes-1）, a target of Notch activation, were reduced by DAPT in a dose-dependent manner. Coincident with this observation, DAPT induced a dose-dependent promotion of constitutive Caspase-3 in Tca8113 cells. Conclusion DAPT may have a therapeutic value for human tongue carcinoma. Moreover, the effects of DAPT in tumor inhibition may arise partly via the modulation of Notch- 1 and Caspase-3.展开更多
基金funded by the National Natural Science Foundation of China(30801304)Specialized Research Fund for the Doctoral Program of Higher Education(20070610062)+1 种基金Opening Funding of the State Key Laboratory of Oral Diseases, Sichuan University(SKLOD011)the Applied Fundarmental Project of Sichuan Province(2008 JY0028-2)
文摘Aim To investigate the effect of DAPT （γ-secretase inhibitor） on the growth of human tongue carcinoma cells and to determine the molecular mechanism to enable the potential application of DAPT to the treatment of tongue carcinoma. Methodology Human tongue carcinoma Tca8113 cells were cultured with DAPT. Cell growth was determined using Indigotic Reduction method. The cell cycle and apoptosis were analyzed by flow cytometry. Real-time PCR and Immuno-Fluorescence （IF） were employed to determine the intracellular expression levels. Results DAPT inhibited the growth of human tongue carcinoma Tca8113 cells by inducing G0-G1 cell cycle arrest and apoptosis, The mRNA levels of Hairy/Enhancer of Split-1 （Hes-1）, a target of Notch activation, were reduced by DAPT in a dose-dependent manner. Coincident with this observation, DAPT induced a dose-dependent promotion of constitutive Caspase-3 in Tca8113 cells. Conclusion DAPT may have a therapeutic value for human tongue carcinoma. Moreover, the effects of DAPT in tumor inhibition may arise partly via the modulation of Notch- 1 and Caspase-3.
